The role of familiarity neurocircuitry in novelty seeking

熟悉性神经回路在寻求新奇事物中的作用

基本信息

批准号：
10633147
负责人：
ANDREW R TAPPER
金额：
$ 48.69万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10633147
关键词：
5-Hydroxytryptophan Acute Address Affect Animal Model Anxiety Area Behavior Behavioral Biological Assay Biophysics Brain Cause of Death Cessation of life Consumption Country Cre lox recombination system Data Disease Dopamine Dopamine Receptor Dose Drug Addiction Electrophysiology (science)Exploratory Behavior Familiarity Foundations Gene Delivery Genes Genetic study Goals Health Human Immunohistochemistry In Situ Hybridization Individual Intake Knowledge Link Mediating Molecular Molecular Biology Motivation Mus Neurons Neurotransmitters Nicotine Nicotine Dependence Nicotine Withdrawal Overdose Personality Traits Pharmaceutical Preparations Pharmacology Pharmacotherapy Publishing Receptor Signaling Rewards Role Serotonin Shapes Signal Transduction Slice Social Conditions Societies Stimulus System Testing Therapeutic United States Ventral Tegmental Area Viral Withdrawal Symptom Work addiction behavior influence behavioral response cigarette smoking conditioned place preference cost experimental study insight interpeduncular nucleus neural circuit neuronal circuitry neuropsychiatric disorder nicotine cessation novel novel therapeutic intervention optogenetics patch clamp preference prevent preventable death receptor response selective expression social trait

项目摘要

Project Summary/Abstract Identifying factors that may predispose individuals to developing addiction is a critical component in understanding the basis of the disease. The most common personality traits associated with addiction include heightened novelty seeking and preference, which are associated with increased exploratory behavior in response to novel stimuli and more interaction with novel stimuli compared to familiar stimuli when given a choice, respectively. Genetic studies have linked novelty seeking with the dopamine (DA) neurotransmitter system, as well as genes involved in serotonin (5-hydroxytryptophan, 5HT) signaling. However, the interaction between 5HT and DA in brain areas and neuronal circuits involved in novelty seeking and preference are poorly understood. Recently, we have shown that the interpeduncular nucleus (IPN) is critically involved in novelty seeking and preference. Specifically, activation of IPN GABAergic neurons acts as a brake to reduce exploration of novel stimuli as they become familiar. Our published and preliminary data indicate that the IPN receives DAergic and 5HTergic inputs from the ventral tegmental area (VTA) and median raphe (MR), respectively. We hypothesize that these two IPN afferents interact to affect novelty seeking and preference through modulation of familiarity signaling. Aim 1 will combine optogenetics and behavior in mice to test the hypothesis that activation of a VTA→IPN DAergic circuit prevents familiarity signaling to increase novelty seeking and motivation to explore novel stimuli. Aim 2 will use a similar approach to determine how 5HT receptor signaling through serotonergic input from the MR to the IPN may influence the behavioral response to novel and familiar stimuli. Finally, Aim 3 will use a biophysical and optogenetic approach to determine how 5HT and DA interact in the IPN and how this controls novelty preference. The results from the proposed experiments should yield significant insight into circuits critical for novelty seeking and preference and elucidate new mechanisms underlying behavioral traits associated with addiction.

项目摘要/摘要识别可能使个人易于发展成瘾的因素是关键的组成部分了解疾病的基础。与成瘾相关的最常见人格特征包括新颖的寻求和偏好与探索行为的增加有关与熟悉的刺激相比，与熟悉的刺激相比，对新型刺激的反应和更多的相互作用选择分别。遗传研究已将寻求新颖性与多巴胺（DA）神经递质联系起来系统以及涉及5-羟色胺（5-Hydroxyptypophan，5HT）信号的基因。但是，相互作用在大脑区域的5HT和DA之间以及参与新颖和偏爱的神经元电路之间理解不佳。最近，我们已经表明，插道核（IPN）至关重要寻求和偏好。特别是，IPN GABA能神经元的激活充当减少的制动随着新颖刺激的探索，它们变得熟悉。我们已发布的初步数据，表明IPN 从腹侧盖区域（VTA）和中位raphe（MR）接收DAERGIC和5HTERGIC输入，分别。我们假设这两个IPN传入相互作用以影响新颖性寻求和偏好通过调制熟悉信号传导。 AIM 1将结合小鼠的光遗传学和行为，以测试 VTA→IPN Daergic电路的激活可阻止熟悉信号的假设，以增加新颖性寻求和动力探索新颖的刺激。 AIM 2将使用类似的方法来确定5HT 通过从MR到IPN的血清能输入的接收器信号传导可能会影响对行为的反应新颖而熟悉的刺激。最后，AIM 3将使用生物物理和光学遗传学方法来确定如何 5HT和DA在IPN中相互作用，以及这如何控制新颖性偏好。提议的结果实验应对电路的重大见解，对于寻求新颖和偏好至关重要的电路以及阐明与成瘾相关的行为特征的新机制。